Chronological Profiling for Paleography

This paper approaches manuscript dating from a Bayesian perspective. Prior work on paleographic date recovery has generally sought to predict a single date for a manuscript. Bayesian analysis makes it possible to estimate a probability distribution that varies with respect to time. This in turn enables a number of alternative analyses that may be of more use to practitioners. For example, it may be useful to identify a range of years that will include a document’s creation date with a particular confidence level. The methods are demonstrated on a selection of Syriac documents created prior to 1300 CE

Biological Consequences of Ancient Gene Acquisition and Duplication in the Large Genome of Candidatus Solibacter usitatus Ellin6076

Members of the bacterial phylum Acidobacteria are widespread in soils and sediments worldwide, and are abundant in many soils. Acidobacteria are challenging to culture in vitro, and many basic features of their biology and functional roles in the soil have not been determined. Candidatus Solibacter usitatus strain Ellin6076 has a 9.9 Mb genome that is approximately 2–5 times as large as the other sequenced Acidobacteria genomes. Bacterial genome sizes typically range from 0.5 to 10 Mb and are influenced by gene duplication, horizontal gene transfer, gene loss and other evolutionary processes. Our comparative genome analyses indicate that the Ellin6076 large genome has arisen by horizontal gene transfer via ancient bacteriophage and/or plasmid-mediated transduction, and widespread small-scale gene duplications, resulting in an increased number of paralogs. Low amino acid sequence identities among functional group members, and lack of conserved gene order and orientation in regions containing similar groups of paralogs, suggest that most of the paralogs are not the result of recent duplication events. The genome sizes of additional cultured Acidobacteria strains were estimated using pulsed-field gel electrophoresis to determine the prevalence of the large genome trait within the phylum. Members of subdivision 3 had larger genomes than those of subdivision 1, but none were as large as the Ellin6076 genome. The large genome of Ellin6076 may not be typical of the phylum, and encodes traits that could provide a selective metabolic, defensive and regulatory advantage in the soil environment

Transformer-based Dual-domain Network for Few-view Dedicated Cardiac SPECT Image Reconstructions

Cardiovascular disease (CVD) is the leading cause of death worldwide, and myocardial perfusion imaging using SPECT has been widely used in the diagnosis of CVDs. The GE 530/570c dedicated cardiac SPECT scanners adopt a stationary geometry to simultaneously acquire 19 projections to increase sensitivity and achieve dynamic imaging. However, the limited amount of angular sampling negatively affects image quality. Deep learning methods can be implemented to produce higher-quality images from stationary data. This is essentially a few-view imaging problem. In this work, we propose a novel 3D transformer-based dual-domain network, called TIP-Net, for high-quality 3D cardiac SPECT image reconstructions. Our method aims to first reconstruct 3D cardiac SPECT images directly from projection data without the iterative reconstruction process by proposing a customized projection-to-image domain transformer. Then, given its reconstruction output and the original few-view reconstruction, we further refine the reconstruction using an image-domain reconstruction network. Validated by cardiac catheterization images, diagnostic interpretations from nuclear cardiologists, and defect size quantified by an FDA 510(k)-cleared clinical software, our method produced images with higher cardiac defect contrast on human studies compared with previous baseline methods, potentially enabling high-quality defect visualization using stationary few-view dedicated cardiac SPECT scanners.Comment: Early accepted by MICCAI 2023 in Vancouver, Canad

Be Healthy in Pregnancy: Exploring factors that impact pregnant women\u27s nutrition and exercise behaviours

Excess gestational weight gain is associated with short- and long-term pregnancy complications. Although a healthy diet and physical activity during pregnancy are recommended and shown to reduce the risk of complications and improve outcomes, adherence to these recommendations is low. The aims of this study were to explore women\u27s view of nutrition and physical activity during pregnancy and to describe barriers and facilitators experienced in implementing physical activity and nutrition recommendations. In a substudy of the Be Healthy in Pregnancy randomized trial, 20 semistructured focus groups were conducted with 66 women randomized to the control group when they were between 16 and 24 weeks gestation. Focus groups were recorded, transcribed verbatim, coded and thematically analysed. The results indicate that women felt motivated to be healthy for their baby, but competing priorities may take precedence. Participants described limited knowledge and access to information on safe physical activity in pregnancy and lacked the skills needed to operationalize both physical activity and dietary recommendations. Women\u27s behaviours regarding diet and physical activity in pregnancy were highly influenced by their own and their peers\u27 beliefs and values regarding how weight gain impacted their health during pregnancy. Pregnancy symptoms beyond women\u27s control such as fatigue and nausea made physical activity and healthy eating more challenging. Counselling from care providers about nutrition and physical activity was perceived as minimal and ineffective. Future interventions should address improving counselling strategies and address individual\u27s beliefs around nutrition and activity in pregnancy

Collective Sensemaking Around COVID-19: Experiences, Concerns, and Agendas for our Rapidly Changing Organizational Lives

Uncertainty is at the forefront of many crises, disasters, and emergencies, and the COVID-19 pandemic is no different in this regard. In this forum, we, as a group of organizational communication scholars currently living in North America, engage in sensemaking and sensegiving around this pandemic to help process and share some of the academic uncertainties and opportunities relevant to organizational scholars. We begin by reflexively making sense of our own experiences with adjusting to new ways of working during the onset of the pandemic, including uncomfortable realizations around privilege, positionality, race, and ethnicity. We then discuss key concerns about how organizations and organizing practices are responding to this extreme uncertainty. Finally, we offer thoughts on the future of work and organizing informed by COVID-19, along with a list of research practice considerations and potentially generative research questions. Thus, this forum invites you to reflect on your own experiences and suggests future directions for research amidst and after a cosmology event

FANCJ/BACH1 Acetylation at Lysine 1249 Regulates the DNA Damage Response

BRCA1 promotes DNA repair through interactions with multiple proteins, including CtIP and FANCJ (also known as BRIP1/BACH1). While CtIP facilitates DNA end resection when de-acetylated, the function of FANCJ in repair processing is less well defined. Here, we report that FANCJ is also acetylated. Preventing FANCJ acetylation at lysine 1249 does not interfere with the ability of cells to survive DNA interstrand crosslinks (ICLs). However, resistance is achieved with reduced reliance on recombination. Mechanistically, FANCJ acetylation facilitates DNA end processing required for repair and checkpoint signaling. This conclusion was based on the finding that FANCJ and its acetylation were required for robust RPA foci formation, RPA phosphorylation, and Rad51 foci formation in response to camptothecin (CPT). Furthermore, both preventing and mimicking FANCJ acetylation at lysine 1249 disrupts FANCJ function in checkpoint maintenance. Thus, we propose that the dynamic regulation of FANCJ acetylation is critical for robust DNA damage response, recombination-based processing, and ultimately checkpoint maintenance

The Vaginal Microbiome: Disease, Genetics and the Environment

The vagina is an interactive interface between the host and the environment. Its surface is covered by a protective epithelium colonized by bacteria and other microorganisms. The ectocervix is nonsterile, whereas the endocervix and the upper genital tract are assumed to be sterile in healthy women. Therefore, the cervix serves a pivotal role as a gatekeeper to protect the upper genital tract from microbial invasion and subsequent reproductive pathology. Microorganisms that cross this barrier can cause preterm labor, pelvic inflammatory disease, and other gynecologic and reproductive disorders. Homeostasis of the microbiome in the vagina and ectocervix plays a paramount role in reproductive health. Depending on its composition, the microbiome may protect the vagina from infectious or non-infectious diseases, or it may enhance its susceptibility to them. Because of the nature of this organ, and the fact that it is continuously colonized by bacteria from birth to death, it is virtually certain that this rich environment evolved in concert with its microbial flora. Specific interactions dictated by the genetics of both the host and microbes are likely responsible for maintaining both the environment and the microbiome. However, the genetic basis of these interactions in both the host and the bacterial colonizers is currently unknown. _Lactobacillus_ species are associated with vaginal health, but the role of these species in the maintenance of health is not yet well defined. Similarly, other species, including those representing minor components of the overall flora, undoubtedly influence the ability of potential pathogens to thrive and cause disease. Gross alterations in the vaginal microbiome are frequently observed in women with bacterial vaginosis, but the exact etiology of this disorder is still unknown. There are also implications for vaginal flora in non-infectious conditions such as pregnancy, pre-term labor and birth, and possibly fertility and other aspects of women’s health. Conversely, the role of environmental factors in the maintenance of a healthy vaginal microbiome is largely unknown. To explore these issues, we have proposed to address the following questions:

*1.	Do the genes of the host contribute to the composition of the vaginal microbiome?* We hypothesize that genes of both host and bacteria have important impacts on the vaginal microbiome. We are addressing this question by examining the vaginal microbiomes of mono- and dizygotic twin pairs selected from the over 170,000 twin pairs in the Mid-Atlantic Twin Registry (MATR). Subsequent studies, beyond the scope of the current project, may investigate which host genes impact the microbial flora and how they do so.
*2.	What changes in the microbiome are associated with common non-infectious pathological states of the host?* We hypothesize that altered physiological (e.g., pregnancy) and pathologic (e.g., immune suppression) conditions, or environmental exposures (e.g., antibiotics) predictably alter the vaginal microbiome. Conversely, certain vaginal microbiome characteristics are thought to contribute to a woman’s risk for outcomes such as preterm delivery. We are addressing this question by recruiting study participants from the ~40,000 annual clinical visits to women’s clinics of the VCU Health System.
*3.	What changes in the vaginal microbiome are associated with relevant infectious diseases and conditions?* We hypothesize that susceptibility to infectious disease (e.g. HPV, _Chlamydia_ infection, vaginitis, vaginosis, etc.) is impacted by the vaginal microbiome. In turn, these infectious conditions clearly can affect the ability of other bacteria to colonize and cause pathology. Again, we are exploring these issues by recruiting participants from visitors to women’s clinics in the VCU Health System.

Three kinds of sequence data are generated in this project: i) rDNA sequences from vaginal microbes; ii) whole metagenome shotgun sequences from vaginal samples; and iii) whole genome shotgun sequences of bacterial clones selected from vaginal samples. The study includes samples from three vaginal sites: mid-vaginal, cervical, and introital. The data sets also include buccal and perianal samples from all twin participants. Samples from these additional sites are used to test the hypothesis of a per continuum spread of bacteria in relation to vaginal health. An extended set of clinical metadata associated with these sequences are deposited with dbGAP. We have currently collected over 4,400 samples from ~100 twins and over 450 clinical participants. We have analyzed and deposited data for 480 rDNA samples, eight whole metagenome shotgun samples, and over 50 complete bacterial genomes. These data are available to accredited investigators according to NIH and Human Microbiome Project (HMP) guidelines. The bacterial clones are deposited in the Biodefense and Emerging Infections Research Resources Repository ("http://www.beiresources.org/":http://www.beiresources.org/). 

In addition to the extensive sequence data obtained in this study, we are collecting metadata associated with each of the study participants. Thus, participants are asked to complete an extensive health history questionnaire at the time samples are collected. Selected clinical data associated with the visit are also obtained, and relevant information is collected from the medical records when available. This data is maintained securely in a HIPAA-compliant data system as required by VCU’s Institutional Review Board (IRB). The preponderance of these data (i.e., that judged appropriate by NIH staff and VCU’s IRB are deposited at dbGAP ("http://www.ncbi.nlm.nih.gov/gap":http://www.ncbi.nlm.nih.gov/gap). Selected fields of this data have been identified by NIH staff as ‘too sensitive’ and are not available in dbGAP. Individuals requiring access to these data fields are asked to contact the PI of this project or NIH Program Staff. 
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Structured diet and exercise guidance in pregnancy to improve health in women and their offspring: study protocol for the Be Healthy in Pregnancy (BHIP) randomized controlled trial

BackgroundEvidence from epidemiological and animal studies support the concept of programming fetal, neonatal, and adult health in response to in utero exposures such as maternal obesity and lifestyle variables. Excess gestational weight gain (GWG), maternal physical activity, and sub-optimal and excess nutrition during pregnancy may program the offspring\u27s risk of obesity. Maternal intake of dairy foods rich in high-quality proteins, calcium, and vitamin D may influence later bone health status. Current clinical practice guidelines for managing GWG are not founded on randomized trials and lack specific active intervention ingredients. The Be Healthy in Pregnancy (BHIP) study is a randomized controlled trial (RCT) designed to test the effectiveness of a novel structured and monitored Nutrition + Exercise intervention in pregnant women of all pre-pregnancy weight categories (except extreme obesity), delivered through prenatal care in community settings (rather than in hospital settings), on the likelihood of women achieving recommended GWG and a benefit to bone status of offspring and mother at birth and sixmonths postpartum.MethodsThe BHIP study is a two-site RCT that will recruit up to 242 participants aged \u3e18years at 12-17 weeks of gestation. After baseline measures, participants are randomized to either a structured and monitored Nutrition + Exercise (intervention) or usual care (control) program for the duration of their pregnancy. The primary outcome of the study is the percent of women who achieve GWG within the Institute of Medicine (IOM) guidelines. The secondary outcomes include: (1) maternal bone status via blood bone biomarkers during pregnancy; (2) infant bone status in cord blood; (3) mother and infant bone status measured by dual-energy absorptiometry scanning (DXA scan) at sixmonths postpartum; (4) other measures including maternal blood pressure, blood glucose and lipid profiles, % body fat, and postpartum weight retention; and (5) infant weight z-scores and fat mass at sixmonths of age.DiscussionIf effective, this RCT will generate high-quality evidence to refine the nutrition guidelines during pregnancy to improve the likelihood of women achieving recommended GWG. It will also demonstrate the importance of early nutrition on bone health in the offspring

Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model

OBJECTIVES: The potential for beneficial effects of adipose-derived stem cells (ASCs) on myocardial perfusion and left ventricular dysfunction in myocardial ischemia (MI) has not been tested following intravenous delivery. METHODS: Surviving pigs following induction of MI were randomly assigned to 1 of 3 different groups: the placebo group (n = 7), the single bolus group (SB) (n = 7, 15 × 10(7) ASCs), or the divided dose group (DD) (n = 7, 5 × 10(7) ASCs/day for three consecutive days). Myocardial perfusion defect area and coronary flow reserve (CFR) were compared during the 28-day follow-up. Also, serial changes in the absolute number of circulating CD4(+) T and CD8(+) T cells were measured. RESULTS: The increases in ejection fraction were significantly greater in both the SB and the DD groups compared to the placebo group (5.4 ± 0.9%, 3.7 ± 0.7%, and -0.4 ± 0.6%, respectively), and the decrease in the perfusion defect area was significantly greater in the SB group than the placebo group (-36.3 ± 1.8 and -11.5 ± 2.8). CFR increased to a greater degree in the SB and the DD groups than in the placebo group (0.9 ± 0.2, 0.8 ± 0.1, and 0.2 ± 0.2, respectively). The circulating number of CD8(+) T cells was significantly greater in the SB and DD groups than the placebo group at day 7 (3,687 ± 317/µL, 3,454 ± 787/µL, and 1,928 ± 457/µL, respectively). The numbers of small vessels were significantly greater in the SB and the DD groups than the placebo group in the peri-infarct area. CONCLUSIONS: Both intravenous SB and DD delivery of ASCs are effective modalities for the treatment of MI in swine. Intravenous delivery of ASCs, with its immunomodulatory and angiogenic effects, is an attractive noninvasive approach for myocardial rescue

Dorsal hippocampal regulation of memory reconsolidation processes that facilitate drug context-induced cocaine-seeking behavior in rats

Exposure to a cocaine-paired context increases the propensity for relapse in cocaine users and prompts cocaine-seeking behavior in rats. According to the reconsolidation hypothesis, upon context re-exposure, established cocaine-related associations are retrieved and can become labile. These associations must undergo reconsolidation into long-term memory to effect enduring stimulus control. The dorsal hippocampus (DH), dorsolateral caudate-putamen, and dorsomedial prefrontal cortex are critical for the expression of context-induced cocaine seeking, and these brain regions may also play a role in the reconsolidation of cocaine-related memories that promote this behavior. To test this hypothesis, rats were trained to press a lever for un-signaled cocaine infusions (0.2 mg/infusion, IV) in a distinct environmental context (cocaine-paired context), followed by extinction training in a different context (extinction context). Rats were then re-exposed to the cocaine-paired context for 15 min in order to reactivate cocaine-related memories or received comparable exposure to a novel unpaired context. Immediately thereafter, rats received bilateral microinfusions of the protein synthesis inhibitor anisomycin, the sodium channel blocker tetrodotoxin, or vehicle into one of the above brain regions. After additional extinction training in the extinction context, reinstatement of cocaine-seeking behavior (i.e., non-reinforced lever presses) was assessed in the cocaine-paired context. Tetrodotoxin, but not anisomycin, administered into the DH inhibited drug context-induced cocaine-seeking behavior in a memory reactivation-dependent manner. Other manipulations failed to alter this behavior. These findings suggest that the DH facilitates the reconsolidation of associative memories that maintain context-induced cocaine-seeking behavior, but it is not the site of anisomycin-sensitive memory re-stabilization per se